SAT-250 Integrated Concentrations of Cortisol (IC-F) Are Higher in Obese African American (AA) Youth with Type 2 Diabetes (T2D): Evidence for a Maladaptive Change in F Further Exacerbating Dysglycemia?

Introduction: Cortisol (F) has physiologic actions which are antagonistic to insulin. As F has pulsatile secretion and diurnal variation, integrating blood concentrations (IC) over time has been recommended as the most accurate estimate of tissue exposure to circulating hormones. We previously reported that IC-F are suppressed in obese youth without Type 2 diabetes (T2D) compared to lean age matched subjects. We speculated that IC-F suppression was adaptive and potentially reduces insulin resistance. We hypothesize that obese pediatric patients with T2D have increased levels of IC-F compared to those without T2D. Methods: To test this hypothesis we measured IC-F, IC-cortisone (IC-E), IC-C-peptide (IC-CP) and IC-Cortisol Binding Globulin (CBG) in obese self-identified African-American (AA) youth with and without T2D. Patients had indwelling catheters placed and blood was withdrawn half-hourly for 24 hours. A 24-hour IC was made by pooling a small aliquot from each half-hourly sample. The IC for each hormone was assayed from the pool. In two subjects one with and one without diabetes only a 12-hour pooled sample was available. Pooled samples of F, E, CBG, and CP were assayed by standard methods. One tailed comparison between groups was used as our a priori hypothesis was that counter regulatory hormones would be increased and IC-CP lower in T2D. A 24 h urine was also collected for F and E metabolites which were assayed at the Steroid Endocrinology Unit, University College London Hospitals, London, UK. Results. The two groups, obese without T2D (n=10) and obese with T2D (n=9) respectively, were similar in age (14.61± 2.03 vs 15.10± 2.89, p=0.67), BMI % (99.45 ±0.24 vs 98.10± 1.91, p= 0.07), and gender distribution (F/M 8/2 vs 6/3, p=0.63). IC-F (3.96± 1.22 μg/dl vs 5.79 ±1.70 μg/dl, p=0.017), IC-E (0.82 ± 0.39 μg/dl vs 1.13± 0.32 μg/dl, p=0.038) were higher in T2D patients while IC-CP (4.36±1.12 ng/ml; vs 2.33± 0.89 ng/ml, p=0.0005) was lower in T2D. There was no difference in IC-CBG (2.56 ±0.48 mg/dl vs 2.84±0.58 mg/dl, p=0.260). IC-F was correlated with IC-E (r=0.45, p=0.047). IC-F tended to be higher for any given IC-E level in T2D patients. There was no difference between groups for the urine F and E metabolites. Conclusions: 1) IC-F and IC-E levels are higher in T2D than in obese youth without T2D and may represent a maladaptive change exacerbating hyperglycemia and other metabolic complications. 2) IC-F tends to be higher at any given level of IC-E in T2D, which may occur by altered 11βHSD interconversion of F and E. However, a change in HPA axis tone cannot be ruled out. 3) Plasma IC measures of F and E may be more sensitive than urine metabolites for detecting changes associated with T2D. 4) Preventing increased IC-F in T2D may be a potential target for therapeutic intervention.Sources of Research Support: NIH, Endocrine Fellows Foundation, Inter-institutional funding.